Genome-Wide Association Study of Lean Body Mass Response to Resistance Training in Young Asians

Resistance training (RT) is an established intervention for increasing lean body mass (LBM), individual hypertrophic responses exhibit significant heterogeneity, largely influenced by genetic factors. This genome-wide association study (GWAS) aimed to identify novel genetic variants associated with changes in lean body mass (∆LBM) following RT and to develop a genetic predisposition score (GPS) for predicting LBM trainability.

A total of 187 sedentary adults (51.3% female, mean age 21.5 ± 2 years) completed a supervised 12-week periodized RT programme. The protocol involved squats and bench presses at 70% 1-repetition maximum (5 sets × 10 repetitions; 2-min rest) performed twice weekly. ∆LBM was precisely quantified using dual-energy X-ray absorptiometry (DEXA) before and after the intervention. Genotyping was performed on venous blood-derived DNA using the Illumina Global Screening Array-24v1-0. GWAS for ∆LBM was conducted using linear regression in PLINK 1.09, adjusted for baseline LBM, body mass index (BMI), age, region and sex (genome-wide significance threshold: p < 5 × 10^-8). A weighted GPS was subsequently constructed in SAS 9.3 based on significantly associated variants.

The RT programme elicited significant LBM gains across the cohort (p < 0.01) accompanied by high interindividual variability (∆LBM coefficient of variation = 0.84). GWAS identified nine novel single-nucleotide polymorphisms (SNP) significantly associated with ∆LBM (p < 5 × 10^-8): rs10212396, rs12519717, rs12055037, rs2131183, rs75968146, rs4370982, rs74038095, rs73966436, and rs12625907. The developed GPS explained 27.7% of the observed ∆LBM variance (p < 0.001). Bioinformatic annotation revealed that rs10212396 is located near the ROBO2 locus-a gene potentially implicated in muscular adaptation, though the specific functional roles of most proximal genes identified remain to be fully characterized.

This study, representing the first GWAS of RT-induced LBM adaptation, successfully identified nine novel genetic variants and establishes a robust GPS that accounts for 27.7% of interindividual variation in LBM response. These findings provide foundational genetic markers crucial for deciphering the mechanisms underlying muscle hypertrophy and significantly advance the prospects for developing personalized exercise prescriptions.